Abstract

Background

More than half of the patients diagnosed with mCRC are elderly (70+ years). Older patients comprise a heterogeneous group, they are underrepresented in clinical trials, and knowledge about the best treatment strategy in patients who are not candidates for standard full-dose combination therapy is sparse and it is uncertain whether full dose or reduced dose chemotherapy is the optimal strategy. The oral prodrug S-1 (Teysuno®) is well tolerated as monotherapy and in combinations and could be an ideal drug for older patients (Winther et al, Acta Oncol 2015), but more data to predict toxicity and efficacy is needed. The NORDIC9 study will add knowledge on how to select and tailor the optimal treatment strategy for older mCRC patient who are not candidates for standard combination therapy.

Trial design

NORDIC9 is a randomized phase II trial exploring treatment of older mCRC patients (≥ 70 years) who are not candidates to full-dose combination therapy, by comparing full dose monotherapy (S-1 30 mg/m2 twice daily days 1-14 every 3 weeks, followed by second line irinotecan 250-350 mg/m2 iv day 1 every 3 weeks or 180-240 mg/m2 iv day 1 every 2 weeks) with reduced dose (80%) combination therapy regimen (S-1 20 mg/m2 days 1-14 + oxaliplatin 100 mg/m2 iv day 1 every 3 weeks, followed by second line S-1 20 mg/m2 days 1-14 + irinotecan 180 mg/m2 day 1 every 3 week). Bevacizumab (7.5 mg/kg) may be added at the discretion of the treating clinician. Geriatric screening tools (G-8, VES-13, Timed-Up-and-Go, Grip strength), Charlson Comorbidity Index and Quality of Life (EORTC QLQ-C30) will be evaluated at baseline. Blood samples and tumor tissue will be collected to investigate predictive value. Enrollment was initiated in March 2015, and 52 patients are currently included. Primary endpoint is progression-free survival and secondary endpoints are time-to-failure of strategy, overall survival, response rate, toxicity, and correlations between biomarkers, pre-treatment characteristics and geriatric assessments.

Clinical trial identification

EudraCT 2014-000394-39

Legal entity responsible for the study

Clinical Research Unit, Department of Oncology, Odense University Hospital